Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival
Summary Although TNFRSF17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B‐cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multipl...
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| Published in | British journal of haematology Vol. 158; no. 6; pp. 727 - 738 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford
Blackwell Publishing Ltd
01.09.2012
Blackwell |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Summary
Although TNFRSF17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B‐cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age‐matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients. |
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| AbstractList | Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age-matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients. Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age-matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients.Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age-matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients. Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age-matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P=0.0157) and healthy subjects (P<0.0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P=0.0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P =0.001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients. Although TNFRSF 17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B ‐cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma ( MM ) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients ( n = 209), monoclonal gammopathy of undetermined significance ( MGUS ) individuals ( n = 23) and age‐matched controls ( n = 40). BCMA was detected in the serum of untreated MM patients ( n = 50) and levels were higher than in MGUS patients ( P = 0·0157) and healthy subjects ( P < 0·0001). Serum BCMA levels were higher among patients with progressive disease ( n = 80) compared to those with responsive disease ( n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median ( P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA , and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients. Summary Although TNFRSF17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B‐cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age‐matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients. |
| Author | Swift, Regina A. Waterman, Gabriel N. Robinson, Austin Chen, Haiming Nichols, Cydney M. Vescio, Robert A. Li, Jennifer Kirk, Dylan T. Wang, Cathy S. Boccia, Ralph Bonavida, Benjamin Kitto, Alex Li, Mingjie Yellin, Ori Berenson, James R. Ahles, Cameryn P. Dreyer, Marissa P. Sanchez, Eric Crowley, John Madden, Erik |
| Author_xml | – sequence: 1 givenname: Eric surname: Sanchez fullname: Sanchez, Eric organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 2 givenname: Mingjie surname: Li fullname: Li, Mingjie organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 3 givenname: Alex surname: Kitto fullname: Kitto, Alex organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 4 givenname: Jennifer surname: Li fullname: Li, Jennifer organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 5 givenname: Cathy S. surname: Wang fullname: Wang, Cathy S. organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 6 givenname: Dylan T. surname: Kirk fullname: Kirk, Dylan T. organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 7 givenname: Ori surname: Yellin fullname: Yellin, Ori organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 8 givenname: Cydney M. surname: Nichols fullname: Nichols, Cydney M. organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 9 givenname: Marissa P. surname: Dreyer fullname: Dreyer, Marissa P. organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 10 givenname: Cameryn P. surname: Ahles fullname: Ahles, Cameryn P. organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 11 givenname: Austin surname: Robinson fullname: Robinson, Austin organization: David Geffen School of Medicine, University of California, CA, Los Angeles, USA – sequence: 12 givenname: Erik surname: Madden fullname: Madden, Erik organization: David Geffen School of Medicine, University of California, CA, Los Angeles, USA – sequence: 13 givenname: Gabriel N. surname: Waterman fullname: Waterman, Gabriel N. organization: Keck School of Medicine, University of Southern California, CA, Los Angeles, USA – sequence: 14 givenname: Regina A. surname: Swift fullname: Swift, Regina A. organization: James R. Berenson, MD, Inc, CA, West Hollywood, USA – sequence: 15 givenname: Benjamin surname: Bonavida fullname: Bonavida, Benjamin organization: Department of Microbiology, Immunology and Molecular Genetics, Geffen School of Medicine, University of California, CA, Los Angeles, USA – sequence: 16 givenname: Ralph surname: Boccia fullname: Boccia, Ralph organization: Center for Cancer and Blood Disorders, MD, Bethesda, USA – sequence: 17 givenname: Robert A. surname: Vescio fullname: Vescio, Robert A. organization: Cedars-Sinai Medical Center, CA, Los Angeles, USA – sequence: 18 givenname: John surname: Crowley fullname: Crowley, John organization: Cancer Research and Biostatics, WA, Seattle, USA – sequence: 19 givenname: Haiming surname: Chen fullname: Chen, Haiming organization: Institute for Myeloma & Bone Cancer Research, CA, West Hollywood, USA – sequence: 20 givenname: James R. surname: Berenson fullname: Berenson, James R. email: Correspondence: Dr James R. Berenson, Institute for Myeloma & Bone Cancer Research, 9201 W Sunset Blvd, Suite 300, West Hollywood, CA 90069, USA., jberenson@imbcr.org organization: Institute for Myeloma & Bone Cancer Research, West Hollywood, CA, USA |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26346373$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22804669$$D View this record in MEDLINE/PubMed |
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| Keywords | Immunopathology multiple myeloma Hematology xenografts B-cell maturation antigen Malignant hemopathy Transplantation Heterotransplantation Myeloma Survival In vivo Treatment Immunoglobulinopathy Surgery Lymphoproliferative syndrome Animal Graft Serum Cancer |
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| Notes | ArticleID:BJH9241 ark:/67375/WNG-G741KNT4-8 istex:A411C21A0026FEB98103C0E12959E8983158B3C5 Fig S1. Membrane bound BCMA expression on primary MM cells. Fig S2. Serum and supernatant BCMA level correlation. Fig S3. Changes in serum BCMA levels were found to correlate with changes in individual patient's clinical status in response to anti-MM treatment. Fig S4. Kaplan-Meier survival of MM patients with serum BCMA levels in the highest quartile (25%). Table SI. Serum BCMA levels do not correlate with the use of specific anti-MM agents. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
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Although TNFRSF17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B‐cell malignancies, it has not been found in... Although TNFRSF 17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B ‐cell malignancies, it has not been found in serum.... Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum.... |
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| SubjectTerms | Animals B-cell maturation antigen B-Cell Maturation Antigen - analysis Biological and medical sciences biomarkers Bone marrow Bone Marrow - chemistry Boronic Acids - therapeutic use Bortezomib Cell Membrane - chemistry Cell survival Culture Media, Conditioned - chemistry Cyclophosphamide Cyclophosphamide - therapeutic use Enzyme-Linked Immunosorbent Assay - methods Flow Cytometry Hematologic and hematopoietic diseases Humans Immunodeficiencies. Immunoglobulinopathies Immunoglobulin G - blood Immunoglobulinopathies Immunopathology in vivo Kaplan-Meier Estimate Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Leukocytes (mononuclear) Lymphocytes B Malignancy Medical sciences Melphalan Mice Mice, SCID Monoclonal gammopathy Monoclonal Gammopathy of Undetermined Significance - blood Multiple myeloma Multiple Myeloma - drug therapy Multiple Myeloma - metabolism Multiple Myeloma - mortality Multiple Myeloma - pathology Neoplasm Proteins - analysis Neoplasm Transplantation Plasma Cells - chemistry Pyrazines - therapeutic use serum Survival Tumor Burden Tumor Cells, Cultured - metabolism Xenografts |
| Title | Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival |
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